A sedentary work force may be at increased risk of future cardiovascular disease. Exercise at the worksite has been advocated, but effects on endothelium as a biomarker of risk and relation to weight loss, lipid changes or circulating endothelial progenitor cells (EPCs) have not been reported. Seventytwo office and laboratory (26 with body-mass index [BMI] > 30 kg/m 2 ) employees (58 women; average age 45 years; range: 22-62 years) completed 3 months of participation in the National Heart, Lung, and Blood Institute's "Keep the Beat" program, with determination of vital signs, laboratory data and peak oxygen consumption (VO 2 ) during treadmill exercise. Brachial artery endothelium was tested by flow-mediated dilation (FMD), which at baseline was inversely associated with Framingham risk score (r=-0.3689, P<0.0001). EPCs were quantified by colony assay. With exercise averaging 98±47 (mean±SD) minutes each work week, there was improvement in FMD (from 7.8 ±3.4 to 8.5±3.0%, P=0.0096) and peak VO 2 (+1.2±3.1 mL O 2 /kg/min; P=0.0028), with reduction in diastolic blood pressure (-2±8 mmHg; P=0.0478), total cholesterol (-8±25 mg/dL, P=0.0131), lowdensity lipoprotein (LDL) cholesterol (-7±19 mg/dL, P=0.0044), but with marginal reduction in weight (-0.5±2.1 kg, P=0.0565). By multiple regression modeling, lower baseline FMD, greater age, reductions in total and LDL cholesterol and diastolic blood pressure, and increases in EPC colonies and peak VO 2 were jointly statistically significant predictors of change in FMD and accounted for 47% of the variability in FMD improvement with program participation. Results were similar when modeling was performed for women only. By contrast, neither adiposity at baseline nor change in weight were predictors of improved endothelial function. In conclusion, daily exercise achievable in the worksite by employees with sedentary occupations improves endothelial function-even with absence of weight loss--which may decrease cardiovascular risk, if sustained. Keywords endothelium; nitric oxide; obesity; lipoproteins; exercise Exercise has been associated with multiple health benefits, including favorable effects on lipids, blood pressure, insulin sensitivity and endothelial function 1-5 , yet almost two-thirds of